Department of Medicinal Chemistry and Molecular Pharmacology Personnel - David A. Colby

David A. Colby, Pharm.D., Ph.D. Assistant Professor of Medicinal Chemistry and Molecular Pharmacology Phone: (765) 496-3962 E-mail: dcolby@purdue.edu Lab webpage: http://people.pharmacy.purdue.edu/~dcolby/ Full directory listing

Education

Research: Medicinal Chemistry, Drug Discovery and Synthesis

The emergence of drug-resistant diseases has contributed to a growing need to develop new and innovative treatments for patients afflicted with these disease states. Our research interests are directed toward key therapeutic areas, such as cancer, which is one of the most prominent and deadly diseases when drug-resistance is present. Natural products have traditionally provided a rich source of drugs for many diseases, including cancer. In our laboratory, we seek to use natural products as potential leads for drug discovery in drug-resistant cancer. In order to accomplish these objectives, we will blend the science of medicinal chemistry and synthetic organic chemistry through the use of natural products chemistry, natural product synthesis, and the design of structurally-related analogues for structure-activity investigations. Specifically, we aim to selectively modify the complex structure of natural products and simultaneously understand the effects on biological activity. Natural products, such as parthenolide, santonin, and sclareolide, will be some of the targets that we will investigate to create new leads for drug-resistant cancers.

Representative Publications

Han, C.; Salyer, A. E.; Kim, E. H.; Jiang, X.; Jarrard, R. E.; Powers, M. S.; Kirchhoff, A. M.; Salvador, T. K.; Chester, J. A.; Hockerman, G. H.; Colby, D. A. Evaluation of Difluoromethyl Ketones as Agonists of the gamma-Aminobutyric Acid Type B (GABA-B) Receptor. J. Med. Chem. 2013, 56, 2456–2465. DOI: 10.1021/jm301805e

Riofski, M. V.; Hart, A. D.; Colby, D. A. Amidinate Salt of Hexafluoroacetone Hydrate for the Preparation of Fluorinated Compounds by the Release of Trifluoroacetate. Org. Lett. 2013, 15, 208–211. DOI: 10.1021/ol303291x

Woods, J. R.; Mo, H.; Bieberich, A. A.; Alavanja, T.; Colby, D. A. Amino-derivatives of the Sesquiterpene Lactone Class of Natural Products as Prodrugs. MedChemComm 2013, 4, 27–33. [New Talent themed issue] DOI: 10.1039/c2md20172k

Han, C.; Kim, E. H.; Colby, D. A. Cleaving Carbon-Carbon Bonds by the Release of Trifluoroacetate to Remodel Molecules and Assemble Fluorinate Structures. Synlett 2012, 23, 1559–1563. DOI: 10.1055/s-0031-1291156

Woods, J. R.; Mo, H.; Bieberich, A. A.; Alavanja, T.; Colby, D. A. Fluorinated Amino-Derivatives of the Sesquiterpene Lactone, Parthenolide, as 19F NMR Probes in Deuterium-Free Environments. J. Med. Chem. 2011, 54, 7934–7941. DOI: 10.1021/jm201114t

John, J. P.; Colby, D. A. Synthesis of α-Halo-α,α-difluoromethyl Ketones by a Trifluoroacetate Release/Halogenation Protocol. J. Org. Chem. 2011, 76, 9163-9168. DOI: 10.1021/jo2017179

Riofski, M. V.; John, J. P.; Zheng, M. M.; Kirshner, J.; Colby, D. A. Exploiting the Facile Release of Trifluoroacetate for the α-Methylenation of the Sterically Hindered Carbonyl Groups on (+)-Sclareolide and (-)-Eburnamonine. J. Org. Chem. 2011, 76, 3676-3683. DOI: 10.1021/jo102114f

Han, C.; Kim, E. H.; Colby, D. A. Cleavage of Carbon−Carbon Bonds through the Mild Release of Trifluoroacetate: Generation of α,α-Difluoroenolates for Aldol Reactions. J. Am. Chem. Soc. 2011, 133, 5802-5805. DOI: 10.1021/ja202213f

Gunn, E. J.; Williams, J. T.; Huynh, D. T.; Iannotti, M. J.; Han, C.; Barrios, F. J.; Kendall, S.; Glackin, C. A.; Colby, D. A.; Kirshner, J. The Natural Products, Parthenolide and Andrographolide, Exhibit Anti-Cancer Stem Cell Activity in Multiple Myeloma. Leuk. Lymphoma 2011, 52, 1085-1097 . DOI: 10.3109/10428194.2011.555891

Barrios, F. J.; Zhang, X.; Colby, D. A. Dialkylaluminum N,O-Dimethylhydroxylamine Complex as a Reagent to Mask Reactive Carbonyl Groups in situ from Nucleophiles. Org. Lett. 2010, 12, 5588-5591. DOI: 10.1021/ol102495v
 
Mo, H.; Balko, K. M.; Colby, D. A. A Practical No-Deuterium NMR Method for the Rapid Determination of 1-Octanol/Water Partition Coefficients of Pharmaceutical Agents. Bioorg. Med. Chem. Lett. 2010, 20, 6712-6715. DOI: 10.1016/j.bmcl.2010.08.145
 
Han, C.; Barrios, F. J.; Riofski, M. V.; Colby, D. A. Semisynthetic Derivatives of Sesquiterpene Lactones by Palladium-Catalyzed Arylation of the α-Methylene-gamma-lactone Substructure. J. Org. Chem. 2009, 74, 7176-7179. DOI: 10.1021/jo901533e